CSU

By Allen Yang

January 1, 1970

About this collection

## Chronic Spontaneous Urticaria: Treatment Approaches and Clinical Evidence This collection examines chronic spontaneous urticaria (CSU), a debilitating skin condition characterized by recurrent wheals, angioedema, and pruritus lasting more than 6 weeks. The documents reveal a comprehensive treatment landscape centered on **up-dosing second-generation antihistamines** as the primary therapeutic strategy. ### Key Treatment Insights - **Up-dosing efficacy**: Studies demonstrate that increasing antihistamine doses up to 4x standard amounts (and beyond) provides symptom control in 49-70% of previously unresponsive patients - **Drug-specific evidence**: Fexofenadine, levocetirizine, cetirizine, and bilastine show varying degrees of success, with bilastine demonstrating superior tolerability profiles - **Safety profile**: Side effects remain manageable even at high doses, primarily limited to mild sedation and headache ### Clinical Reality CSU affects 0.5-1% of the population, predominantly working-age adults (20-40 years), with significant quality-of-life impacts including sleep disturbances and work impairment. Despite straightforward diagnostic criteria, patients often experience diagnostic delays. The condition's autoimmune mechanisms remain poorly understood, though IgE autoantibodies and thyroid associations have been identified. ### Treatment Evolution While traditional approaches focus on symptom management, emerging therapies including biologics (omalizumab, ligelizumab), BTK inhibitors, and anti-IL5 antibodies represent the future of CSU treatment for refractory cases.

Curated Sources

E ffi cacy and Safety of Up-dosed Secondgeneration Antihistamines in Uncontrolled Chronic Spontaneous Urticaria: A Review

This review examines the efficacy and safety of up-dosing second-generation antihistamines (sgAHs) in patients with uncontrolled chronic spontaneous urticaria (CSU). The authors conducted a comprehensive literature search across multiple databases and evaluated the evidence using the Oxford Centre for Evidence-Based Medicine (OCEBM) and Strength of Recommendation Taxonomy (SORT) systems. The review suggests that bilastine, fexofenadine, levocetirizine, and cetirizine are recommended for up-dosing in non-responsive CSU patients, with varying levels of evidence and potential adverse effects. The study highlights the importance of up-dosing sgAHs in CSU management, while also noting the need for further large-scale trials to validate the findings.

Key Takeaways

Up-dosing sgAHs is effective in managing CSU, with bilastine, fexofenadine, levocetirizine, and cetirizine showing Grade A recommendation.
The safety profile of up-dosed sgAHs is generally favorable, with no significant dose-dependent increase in adverse effects, except for cetirizine, which may cause sedation.
Further research is needed to determine the efficacy and safety of up-dosing sgAHs in special populations, such as children, geriatric patients, and pregnant or lactating females.

Fexofenadine in higher doses in chronic spontaneous urticaria

The study investigated the efficacy of fexofenadine in higher doses for treating chronic spontaneous urticaria. Thirty-seven patients were enrolled and started with 180 mg of fexofenadine, with the dose doubled to 360 mg and then tripled to 540 mg if symptoms persisted. The urticaria activity score (UAS) was used to measure symptoms. The results showed a significant reduction in UAS from 3.6 at baseline to 0.19 at the end of 4 weeks. Thirteen out of 14 patients who received 540 mg of fexofenadine became asymptomatic. The study concluded that fexofenadine in higher doses effectively controlled urticaria in the majority of patients, with minimal side effects.

Key Takeaways

Higher doses of fexofenadine (up to 540 mg) are effective in controlling chronic spontaneous urticaria in patients who do not respond to standard doses.
The urticaria activity score (UAS) is a useful tool for measuring symptom severity and monitoring treatment response.
Fexofenadine is generally well-tolerated, even at higher doses, with minimal side effects reported in the study.

RESEARCH

This study investigated the effectiveness and safety of antihistamine treatment in patients with chronic spontaneous urticaria (CSU), particularly those who remained unresponsive to standard dosages. The research analyzed 178 CSU patients, finding that up-dosing antihistamines beyond fourfold the standard dose was effective in reducing or eliminating symptoms in 49% of patients who were initially unresponsive to lower doses. The most frequently used antihistamines were second-generation antihistamines (sgAH), with levocetirizine, desloratadine, and fexofenadine being the most common. Side effects were reported in 20% of patients, primarily somnolence, and were not significantly increased when dosages were raised beyond fourfold. The study suggests that up-dosing antihistamines is a feasible therapeutic option that could decrease the need for third-line therapies.

Key Takeaways

Up-dosing antihistamines beyond fourfold can be effective in treating CSU patients unresponsive to standard doses.
The treatment was effective in 49% of patients who did not respond to lower doses, with a median dose of eightfold.
Side effects were reported in 20% of patients, mainly somnolence, and did not significantly increase with higher dosages.
The study supports considering antihistamine up-dosing as a treatment option before moving to third-line therapies like omalizumab or cyclosporine A.
The findings have implications for reducing the need for more expensive and potentially risky third-line treatments.

REVIEW

Chronic spontaneous urticaria (CSU) is a debilitating condition characterized by recurrent wheals, angioedema, and pruritus, significantly impacting quality of life. Standard therapies include second-generation antihistamines and omalizumab, but many patients remain refractory. This review discusses current treatments and emerging novel therapies for CSU, including biologics and targeted treatments. Current treatments such as cyclosporine, dapsone, dupilumab, and TNF-alpha inhibitors have shown efficacy in some cases. Novel therapies under investigation include anti-IgE monoclonal antibodies (ligelizumab, UB221), Bruton tyrosine kinase inhibitors (fenebrutinib, remibrutinib), anti-IL5 monoclonal antibodies (mepolizumab, benralizumab), and other targeted treatments like tezepelumab and lirentelimab. These emerging therapies offer promising outcomes for CSU patients, with various mechanisms of action and potential benefits. Ongoing clinical trials are evaluating the efficacy and safety of these novel treatments.

Key Takeaways

The review highlights the limitations of current CSU treatments and the need for novel therapies.
Emerging biologics and targeted treatments show promise in improving CSU symptoms and quality of life.
Ongoing clinical trials are crucial for establishing the efficacy and safety of these new treatments.
The diverse mechanisms of action among novel therapies offer potential alternatives for refractory CSU patients.
Further research is necessary to compare the efficacy of different treatment modalities and identify the most effective therapies for CSU.

REVIEW

Chronic spontaneous urticaria (CSU) is a complex skin disease characterized by the spontaneous appearance of wheals, angioedema, or both, for more than 6 weeks. The treatment aim is to achieve and maintain a state of remission, but a large proportion of patients are unable to achieve this. A more realistic definition of 'treatment success' is needed to guide ongoing, long-term disease management for each individual patient. Various patient-reported outcomes (PROs) are used to determine disease activity, disease control, and the impact of CSU on a patient's quality of life (QoL). The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guidelines recommend using UAS7 and/or AAS7 for disease activity, UCT and/or AECT for disease control, and CU-Q2oL and/or AE-QoL for QoL. However, there is a lack of consensus on what constitutes 'treatment success' and how to define it. This review evaluates the most common treatment targets in published literature and clinical trials to provide further direction toward a universal definition of 'treatment success'.

Key Takeaways

A universal definition of 'remission' and 'recurrence' is needed, alongside research into predictors for achieving these states.
Further guidance is needed on when to step down treatment and how to define 'treatment success' in CSU.
PROs should be associated with treatment targets, timepoints, and actions to determine whether current treatment is effective and to facilitate long-term management of CSU.
The impact of CSU on a patient's QoL needs to be assessed, ideally over time, to identify treatment success and inform shared decision-making.
Biomarkers and clinical features may be used to predict disease duration and severity, and response to treatment, but their clinical application remains unclear and requires further research.

Comparative study of ef fi cacy and safety of cetirizine and bilastine in patients of chronic spontaneous urticaria: Open -label, randomized, parallel -group study

This study compared the efficacy and safety of cetirizine and bilastine in patients with chronic spontaneous urticaria (CSU). Seventy patients were randomized to receive either cetirizine 10 mg or bilastine 20 mg once daily for 6 weeks. The primary endpoint was the difference in mean total symptom score (MTSS) at baseline and 6 weeks. Bilastine showed a significant reduction in MTSS compared to cetirizine at 1, 3, and 6 weeks. Bilastine also showed a faster onset of action and fewer adverse events like sedation, headache, and gastric irritation. Both drugs were well tolerated, but bilastine had a more favorable tolerability profile.

Key Takeaways

Bilastine was more efficacious than cetirizine in reducing MTSS in CSU patients, with a faster onset of action at 1 week.
Bilastine had a more favorable tolerability profile, with fewer adverse events like sedation, headache, and gastric irritation.
The study suggests that bilastine is a highly effective H1-antihistamine for CSU treatment, even at the basic dose of 20 mg daily.

REVIEW

Chronic spontaneous urticaria (CSU) is a complex inflammatory skin condition characterized by itchy wheals and angioedema, lasting more than 6 weeks. Diagnosis is primarily based on medical history and limited laboratory tests. Despite its straightforward diagnostic algorithm, patients often wait years for a diagnosis. Current treatments are limited, with approximately half of patients resistant to standard second-generation antihistamines. Omalizumab, a monoclonal antibody, is used as add-on therapy for patients unresponsive to antihistamines. Recent advances in understanding CSU's pathogenesis have led to novel targeted therapies in clinical trials, including Bruton tyrosine kinase inhibitors and anti-KIT monoclonal antibodies. The disease has a significant impact on quality of life, with patients experiencing emotional distress, sleep disturbances, and work impairment. Comorbidities such as thyroid disease, psychiatric disorders, and atopic diseases are common. Effective management requires adherence to best-practice guidelines and a stepwise treatment approach based on disease severity and response to treatment.

Key Takeaways

CSU diagnosis is often delayed due to lack of disease awareness and intermittent symptoms, with patients waiting an average of 2-4 years for diagnosis.
Approximately half of CSU patients are resistant to standard second-generation antihistamines, highlighting the need for alternative treatments.
Omalizumab is effective as add-on therapy for CSU patients unresponsive to antihistamines, but some patients remain symptomatic despite treatment.
Novel therapies targeting mast cells and their mediators, such as Bruton tyrosine kinase inhibitors and anti-KIT monoclonal antibodies, show promise in clinical trials for CSU treatment.
CSU has a substantial negative impact on patients' quality of life, with significant emotional, social, and economic burdens, emphasizing the need for timely and effective management.

PRACTICE | FIVE THINGS TO KNOW ABOUT ...

Chronic spontaneous urticaria is characterized by recurrent hives lasting at least six weeks, affecting 0.5%-1% of the general population, primarily between 20 and 40 years old, with women twice as often as men. The condition significantly impacts quality of life, causing sleep disturbances and affecting job or school performance. Although its pathophysiology is unknown, autoimmune mechanisms involving IgE autoantibodies have been implicated. Diagnosis is based on thorough history and physical examination, with limited initial investigations to exclude underlying conditions. First-line treatment involves second-generation H1-antihistamines for symptomatic relief, with treatment escalation for refractory cases. Referral to a clinical allergist is recommended for third-line treatment options.

Key Takeaways

The condition's impact on quality of life is substantial, necessitating effective management strategies beyond just treating symptoms.
Autoimmune mechanisms are potentially significant in the pathophysiology of chronic spontaneous urticaria, suggesting a complex etiology that may require targeted therapeutic approaches.
The limited understanding of the condition's pathophysiology highlights the need for further research into its causes and potential treatments.
Escalation of treatment beyond standard H1-antihistamine dosing is often required, indicating a need for diverse therapeutic options.
Early referral to specialists for refractory cases can help in managing the condition more effectively.

Frequently Asked Questions

How do the efficacy rates of up-dosed fexofenadine (49% at >4x dosing) compare with bilastine's superior tolerability profile, and what factors should guide clinicians in choosing between these approaches?
Given that CSU affects the working population (ages 20-40) with significant work impairment, how do the UAS7, UCT, and CU-Q2oL scores correlate with actual workplace productivity measures?
What is the relationship between the autoimmune mechanisms mentioned (IgE autoantibodies, thyroid disease associations) and treatment response to specific second-generation antihistamines like levocetirizine versus cetirizine?
How do the emerging biologics (omalizumab, ligelizumab, fenebrutinib, remibrutinib) compare in cost-effectiveness to sustained high-dose antihistamine therapy over 1-5 year treatment periods?
What patterns emerge when comparing the 20% side effect rate in the research study with the specific adverse events reported in the fexofenadine up-dosing study (headache, mild sedation)?
How might the diagnostic delays mentioned in the reviews correlate with treatment resistance patterns and the need for antihistamine up-dosing?
What is the optimal timing for transitioning from up-dosed second-generation antihistamines to third-line therapies like omalizumab based on the treatment success definitions discussed?